The objective of this study is to explore the safety of gamma-irradiated allogeneic TALL-104 cells when placed intracranially into pediatric malignant brain tumor patients. One of the Co-PIs of this application, Dr. Santoli at the Wistar Institute, has developed a powerful cell therapy approach to cancer, which utilizes the human Interleukin-2 (IL-2)-dependent leukemic T cell line TALL-104. TALL-104 cells have markers typical of cytotoxic T cells and display MHC nonrestricted tumoricidal activity. Multiple transfers of gamma-irradiated (non-proliferating) TALL-104 cells in the absence of IL-2 into immunodeficient (SCID) mice implanted with different types of human malignancies have resulted in potent anti-tumor effects against established metastases. The same approach in leukemia- bearing immunocompetent mice has induced regression of advanced disease and protection from further relapses. Direct tumoricidal effects and induction of endogenous anti-tumor immunity is demonstrable. Multiple systemic infusions of high-dose TALL-104 cells into dogs with spontaneous refractory tumors indicate the remarkable anti-tumor efficacy and safety of this novel cell therapy approach in a model more analogous to human. Dr. Santoli has initiated Phase I trials in adults with advanced metastatic breast cancer and in children with solid refractory tumors, where TALL-104 cells are given systemically multiple times. AT UCHSC, Dr. Kruse designed an FDA approved clinical study where alloreactive cytotoxic T lymphocytes are intratumorally placed multiple times into resected brain tumor beds. Two of five patients in whom we have long-term follow-up are alive without evidence of tumor recurrence at 43 and 43 months from the start of the immunotherapy. Although promising, this clinical protocol entails labor intensive methods requiring specialized equipment for generation of the biologic. Additionally, since different donors are used at each of five treatment cycles, the biologic is different at each use. Similar to the alloreactive CTL protocol, the well-defined allogeneic TALL-104 cell line will be implanted multiple times intracranially into children wth refractory brain tumors. The study will be performed as a Phase I trial to determine the effects of dose escalation.